Scientific Method —

Selfish genes may have helped make us human

Pieces of selfish DNA may have helped make the human brain distinct from that …

Alu elements are transposable DNA sequences—jumping genes—that "reproduce" by making a copy of themselves and then inserting that copy into a new spot on the chromosome. Alu elements did this so effectively in the past that they now comprise 10 percent of the human genome, and as such are the most abundant mobile elements in it.

Since they do not encode protein products, they used to be considered "junk DNA" or "selfish DNA," having no apparent function beyond their own replication. Yet, because they contain sequences that resemble canonical portions of genes, thousands of human genes contain pieces derived from them. Recent work in PNAS suggests that they may also play a role in regulating how genes get expressed, and possibly help differentiate humans from other primates.

Shen et al. used a method called RNA-Seq to find and categorize all of the Alu elements expressed in ten different human tissues. They found that Alu exons are found in the messenger RNAs of zinc finger (ZNF) transcription factors (proteins that regulate other genes) at seven times the rate they are found in other types of genes. They are found predominantly in an area known to be important for mRNA stability and protein translation.

ZNFs are one of the largest gene families in humans, with over seven hundred members, and many ZNF genes are primate-specific. ZNF genes underwent rapid expansion and adaptive evolution during primate evolution, and are therefore thought to be key contributors to the gene regulation that defines these lineages.

Like some of these ZNF genes, Alu elements are found only in primates. The researchers found that, in human cerebellum and liver, Alu elements are more common in younger genes than in older ones. But Alu’s preference for ZNF genes over other types held even after controlling for a gene's age; Alu elements were found in ancient as well as recent ZNF genes. They suggest that incorporation of Alu DNA has played a role in the evolution and expansion of ZNF genes in primates.

Recent work reported in PLoS Genetics indicated that the ZNF gene family arose from a small ancestral group of eukaryotic zinc-finger transcription factors through many repeated gene duplications. That's certainly compatible with the idea that Alu elements were involved, since DNA repeats can lead to instabilities that can include duplications.

To check if the presence of Alu sequences in a mRNA affects its translation into protein, Shen et al. compared the translation of fifteen different reporter genes. They made two versions, one lacking an Alu element, the other containing it. In ten of the fifteen, the Alu sequences altered translational efficiency. When they looked at how, they found two distinct molecular mechanisms by which this can occur, but they did not rule out the possibility of additional ones.

Human brains differ from those of other primates: ours are significantly larger, and we have different cognitive abilities. Many ZNF genes are differently expressed in human and chimpanzee brains, and since ZNFs function as transcription factors, it has been suggested that they contribute to the differences between primate species through gene regulation. This new work shows that Alu incorporation is an important mechanism in the evolution of ZNF genes; by regulating the regulators, they may be part of what truly distinguishes monkeys from men.